Fungal Skin Infections - Stony Brook University Hospital

during treatment; this is known as an autoeczematization or dermatophytid (id) eruption. Tinea capitis typically presents as 1 of 6 clinical patterns: gray type, black dot, diffuse scale, pustular type, favus, and kerion. Gray type is characterized by circular patches of alopecia and marked scaling with or without erythema. (4)(8) Black dot presents with patches of alopecia and is dotted with broken hair stubs (“black dots”). Diffuse scale is characterized by widespread scaling and is dandruff-like, with or without erythema. Pustular type presents as alopecia with scattered pustules, scaling, and lymphadenopathy. Favus has distinctive yellow cup-shaped crusting around the hair called scutula, along with patchy alopecia and generalized scale; this variant is extremely rare and not usually seen in the United States. Kerion is a boggy tumor with pustules, lymphadenopathy, erythema, and tenderness. (4)(8) It is the most severe inflammatory response and can be caused by either T tonsurans or M canis. (9) When children present without distinguishing characteristics of tinea capitis such as black dot alopecia or kerion, diagnosis may be simplified by recognizing clusters of symptoms. Hubbard (10) found that children with adenopathy, alopecia, pruritus, and scaling were most likely to have a positive culture. Some dermatologists now use scalp dermoscopy (visualization of scalp and hair shaft with magnification and light) to increase diagnostic accuracy; corkscrew and comma-shaped hairs are frequently seen in fungal scalp infections. (11) Differential Diagnosis Because of its broad and varying symptoms, tinea capitis has a substantial differential diagnosis. Among the possibilities are alopecia areata, atopic dermatitis, bacterial scalp abscess, seborrheic dermatitis, trichotillomania, traction alopecia, psoriasis, lichen planopilaris, lupus erythematosus, syphilis, and Langerhans cell histiocytosis (Table 2). (1)(3)(6) Diagnostic Tests Clinical diagnosis should be confirmed via either potassium hydroxide (KOH) microscopy or culture. Culture is preferable because speciation is provided, allowing determination of the most appropriate treatment option. Polymerase chain reaction (PCR) evaluation of dermatophyte infections has become much more cost effective and “kits” are now available, which is likely to lead to wider availability of this exceedingly rapid and sensitive test in the next few years. At this time, PCR appears more sensitive for nail and skin infections than for hair samples. (12) Wood’s light examination causes Microsporum species to fluoresce, but most infections in North America are caused by T tonsurans, which does not fluoresce. (13) Pathogens that do fluoresce include Microsporum species and Trichophyton schoenleinii. (7) Under microscopic analysis, an infected hair can present with mycelium (mass of fungal hyphae) on the external surface of the hair shaft (ectothrix) or with mycelium within the hair shaft (endothrix). (7) A favus infection presents with fungal hyphae and characteristic airspaces within the hair shaft. (7) Wood’s light analysis takes minutes to complete compared with 1 to 4 weeks required for culture results, which are accompanied by low culture-positive rates, all of which may delay treatment and increase the spread of infection. (10) A reasonable course is to start treating children with typical presentations before culture confirmation, although a culture should be attempted. Samples may be obtained either from plucked hairs or cotton swabs that have been premoistened and rolled over the affected site and are inoculated into transport culture. (14) Kerion (abscesses filled with purulent exudate) should be treated aggressively with systemic antifungal medication pending laboratory results because if left untreated, permanent hair loss and scarring may occur. Unfortunately, the degree of inflammation noted in a kerion is not linked to the fungal burden, and cultures may sometimes be negative. However, every attempt should be made to swab the kerion area as well as other areas of the scalp with a cotton swab. Tinea capitis infection may spread from the scalp to other areas of the body (eg, causing tinea corporis) and secondary bacterial infections (eg, Staphylococcus aureus) may occur. (15) If children are unlikely to have an infection (eg, no adenopathy and scaling), experts recommend confirming infection via KOH microscopy or a culture before treatment. (4) Treatment Figure 1. Tinea capitis. Photo courtesy of Dr Avner Shemer, The Chaim Sheba Medical Center Israel. 10 Systemic treatment is required to penetrate hair shafts. Traditionally, griseofulvin was considered the treatment of choice, (16) but a Cochrane collaborative analysis found that terbinafine, fluconazole, and itraconazole are as effective as Pediatrics in Review Downloaded from http://pedsinreview.aappublications.org/ by guest on February 27, 2017

TABLE 2. Differential Diagnosis of Tinea Capitis (1)(2)(6) DISORDER DISTINGUISHING CHARACTERISTICS OF CLINICAL PRESENTATION Alopecia areata Patches of hair loss; total loss of hair; fine miniature hair growth; exclamation point hairs; can involve eyebrows, eyelashes, beards; possible nail pitting Uncommon: scaling, crusting, inflammation (consider infection, other diagnoses) Atopic dermatitis Personal or family history of atopy, may appear on face Uncommon: alopecia, large posterior occipital or cervical nodes, erythema of scalp usually minimal with diffuse faint scales common Bacterial scalp abscess Culture should be used to distinguish from kerion Seborrheic dermatitis Greasy scaling, typical distribution includes nasolabial folds, hairline, eyebrows, postauricular folds, chest Uncommon: alopecia and significant lymphadenopathy Trichotillomania Often involves eyelashes and eyebrows, hairs of varying lengths, scaling uncommon, large geometric shapes of alopecia present Traction alopecia Hair loss in areas under tension; folliculitis may also be present Psoriasis Gray or silver scaling that extends beyond scalp line, nail pitting, family history, involvement of other sites Lichen planopilaris Often affects skin, mucosa, and nails; no hair follicles seen in areas of hair loss; slowly progressive Lupus erythematosus Involves skin, especially face and sometimes connective tissue of internal organs; discoid lesions can lead to scarring Syphilis Involves other areas of the body, not pruritic, scaling uncommon Langerhans cell histiocytosis May involve buttocks, liver problems causing jaundice, fluid in the belly, bulging eyes or eye problems griseofulvin, with shorter periods of treatment with newer antifungals achieving similar results to griseofulvin. (17) For Trichophyton species, terbinafine is preferable, but this agent is not as effective as griseofulvin for Microsporum species. (17)(18) When a child presents with a lesion highly suspicious for Microsporum species (eg, infected cat or dog at home, and/or lesion fluoresces under Wood’s lamp), griseofulvin should be used. Most experts believe that effective treatment doses of griseofulvin should be higher than advised in the package insert (Table 3). If griseofulvin is not available or terbinafine is preferred, the duration of treatment for Microsporum species may be longer compared to the duration for Trichophyton species. The duration of treatment for terbinafine is generally 4 to 6 weeks, and continuing treatment for 2 weeks after symptoms resolve may be beneficial. (8) Griseofulvin therapy is generally used for 8 weeks, but many experts reevaluate a child after 4 to 6 weeks of therapy to consider discontinuation. Some systemic antifungals, such as itraconazole and fluconazole, have been successfully used for pediatric tinea capitis, but such use is off-label, and a large multinational study investigating fluconazole reported cure rates below those seen with either griseofulvin or terbinafine. (40) Nonetheless, fluconazole has been widely used in children for candidiasis and may be an option when other agents are either not available or not covered by the patient’s insurance plan (Table 3). Adjunctive therapy with either selenium sulfide shampoo (1% or 2.5%) (41) or ketoconazole shampoo should be used to decrease the spread of infection. (1)(42) Because tinea capitis is communicable, children should not attend school or child care until treatment has started. Once treatment has begun, the child may return to school but should not share combs, brushes, helmets, or other items that come in contact with the scalp or play contact sports for 14 days to avoid transmission. (1) Household members should be queried and clinically examined for signs and symptoms if possible and mycologically tested if these exist. The use of selenium sulfide shampoo or ketoconazole shampoo prophylactically (2 times/wk for 2-4 weeks) is controversial, and no clear evidence-based data support its use for this purpose, although some experts recommend this. Some also recommend the same prophylaxis for people outside the home in close contact with the child. (1)(4) Close contacts include other children seen daily, such as in a classroom or child care. Although this process may seem daunting, families at least should be informed so that children can be monitored for signs and symptoms and given the option to engage in prophylactic treatment. In some cases, patients may develop an immune response to the fungus triggered by treatment, known as an id reaction. It often presents as a pruritic, papular, or vesicular rash on the face and body and may be alleviated by Vol. 38 No. 1 Downloaded from http://pedsinreview.aappublications.org/ by guest on February 27, 2017 JANUARY 2017 11

TABLE 3. Antifungal Agents for Fungal Infections in Children ANTIFUNGAL DOSAGE DURATION APPLICABLE INFECTIONS NOTES MONITORING GUIDELINES OTC OR PRESCRIPTION Topical: Butenafine 1% cream, twice hydrochloride daily (19) Ciclopirox Clotrimazole 1 week Tinea corporis, tinea Children 12þ years pedis, tinea cruris OTC Tinea corporis, tinea Safety in children 10 pedis, tinea cruris years has not been established When topical clotrimazole and miconazole fail Onychomycosis Considered safe for 12þ years OTC OTC 2 weeks Tinea corporis, tinea Children 2þ years pedis Tinea cruris Children 2þ years 1-2 weeks Pityriasis versicolor Children 2þ years OTC 0.77% cream, twice 1 week daily (20) 8% lacquer, daily with weekly professional debridement 48 weeks 1% cream, twice daily (21) 1% cream, twice daily (21) 1% cream, twice daily (22) 4 weeks Prescription OTC Efinaconazole 10% solution, daily 48 weeks Onychomycosis Safety and efficacy not established Prescription Ketoconazole shampoo 2% once (23) Once Tinea capitis OTC 2% daily (22) 3-14 days, up to Pityriasis versicolor 4 weeks To decrease spread of infection as an adjunct therapy Safety in children not established See above for safety Following treatment, use monthly for 3 months to prevent recurrence Miconazole Selenium sulphide shampoo 2% cream, twice 4 weeks daily (24) 2% cream, twice 2 weeks daily (24) 2% cream, once or 2 weeks twice daily (22) Tinea corporis, tinea Children 2þ years pedis Tinea cruris Children 2þ years OTC Pityriasis versicolor Children 2þ years OTC To decrease spread of infection as an adjunct therapy Safety in children 12 years has not been established for 2.5% See above for safety Following treatment, use monthly for 3 months to prevent recurrence OTC for 1% 1% or 2.5% 2 times Duration of oral Tinea capitis a week (25) treatment 1% (shampoo) or 2.5% (lotion) daily (22) 1-2 weeks, up to Pityriasis versicolor 4 weeks Tavaborole 5% solution daily 48 weeks Onychomycosis Terbinafine 1% cream twice daily (26) 1-2 weeks Tinea corporis, tinea Children 12þ years pedis, tinea cruris When topical clotrimazole and miconazole fail Pityriasis versicolor Children 12þ years 1% cream once or 1-2 weeks twice daily (22) OTC Safety and efficacy not established OTC Prescription for 2.5% OTC Prescription OTC OTC Continued 12 Pediatrics in Review Downloaded from http://pedsinreview.aappublications.org/ by guest on February 27, 2017

TABLE 3. (Continued ) ANTIFUNGAL APPLICABLE INFECTIONS MONITORING GUIDELINES NOTES OTC OR PRESCRIPTION DOSAGE DURATION Tolnaftate 1% cream twice daily (27) 4 weeks Tinea corporis, tinea Children 2þ years pedis, tinea cruris OTC Urea cream 39% twice daily (28) Not available Tinea pedis Safety in children not established When topical terbinafine and ciclopirox fail OTC Clotrimazole troches 10 mg 5 times a day (29) 2 weeks MC Children 3þ years (need to swallow them properly) Prescription Fluconazole (tablet) 3-6 mg/kg daily (30) 2-3 weeks, additional 2 12 mg/kg daily for weeks after neonates (31) symptoms Loading dose first resolve day 3-6 mg/kg weekly FN: 12 weeks (32) TN: 26 weeks Tinea capitis, tinea corporis, tinea pedis, tinea cruris, MC Onychomycosis For mild-to-severe MC Liver tests, Prescription Extensive or resistant exercise tinea infections when caution if liver not tinea capitis dysfunction Oral: Not approved for onychomycosis See above Griseofulvin* (microsize) 10 mg/kg daily (33) 6-8 weeks tinea Tinea capitis, tinea Children 2þ years up to 20-25 mg/kg capitis, 4-8 corporis, tinea Extensive or resistant daily weeks tinea pedis, tinea cruris tinea infections when pedis not tinea capitis Itraconazole (capsules) 5 mg/kg daily (1)(31) 4-6 weeks MC, tinea capitis, tinea corporis, tinea pedis, tinea cruris, onychomycosis Pulse (1 week on FN: 2 pulses therapy, 3 weeks TN: 3 pulses off) 10-20 kg: 50 mg every other day, 3x/week; 20-30 kg: 100 mg/day; 30-40 kg: 100 mg/day alternating 200 mg/day; 40-50 kg: 200 mg/day; 50 kg: 200 mg 2x/day (32) Nystatin suspension 100,000 U/mL, 4-6 mL, 4 times a day for older children, 2 mL for younger children (34) Terbinafine 125 mg/day for (oral granules) 25 kg 187.5 mg/day for 25-35 kg 250 mg/day for 35 kg (35) Prescription Prescription Safety not established in Liver tests, Prescription children exercise For fluconazolecaution if liver resistant MC dysfunction Extensive or resistant tinea infections when not tinea capitis Efficacy and safety not See above, do Prescription established in children not use if congestive heart failure 48 hours after symptoms resolved MC 6 weeks Tinea capitis, tinea Children 4þ years ALT, AST, do not Prescription use if liver corporis, tinea dysfunction pedis, tinea cruris Extensive or resistant tinea infections when not tinea capitis Continued Prescription Vol. 38 No. 1 Downloaded from http://pedsinreview.aappublications.org/ by guest on February 27, 2017 JANUARY 2017 13

TABLE 3. (Continued ) ANTIFUNGAL APPLICABLE INFECTIONS NOTES MONITORING GUIDELINES OTC OR PRESCRIPTION See above Prescription DOSAGE DURATION Terbinafine (tablets) Same dosage as above FN: 6 weeks TN: 12 weeks Onychomycosis Efficacy and safety not assessed in children Amphotericin B 0.25-1.5 mg/kg daily (36) Based on severity MC Safety in children not Renal, liver, Prescription established hematologic When clotrimazole, tests, monitor nystatin, fluconazole, electrolytes itraconazole fail Anidulafungin 0.75-1.5 mg/kg daily (37)(38) 2 weeks after last positive culture MC Safety not established in children 16 years When clotrimazole, nystatin, fluconazole, itraconazole fail Prescription Caspofungin About 2 weeks, MC Loading dose of may be more 70 mg/m2, followed by 50 mg/m2 daily Safety not established in children 12 months When clotrimazole, nystatin, fluconazole, itraconazole fail Prescription Micafungin 2-3 mg/kg daily for About 2 weeks, MC children 30 kg may be more 2-2.25 mg/kg daily or less for children 30 kg (39) Safety not established in children 4 months When clotrimazole, nystatin, fluconazole, itraconazole fail Prescription ALT¼alanine aminotransferase, AST¼aspartate aminotransferase, FN¼fingernails, MC¼mucocutaneous candidiasis, OTC¼over-the-counter, TN¼toenails. *Griseofulvin is no longer available in Canada. Other than griseofulvin, all of the drugs listed have been approved and are available for use in the United States and Canada, but they are not all indicated for use in children, as specified in the Notes column of the table. This review is limited to the United States and Canada. Information is based on package inserts obtained from the National Institutes of Health, United States National Library of Medicine, DailyMed; United States Food and Drug Administration Approved Drug Products Database; and Health Canada’s Drug Product Database. Please check the regulatory status of each drug in your jurisdiction. Check for current dosing and monitoring guidelines. Table 3 is presented as a guide only. topical corticosteroids and systemic antihistamines. However, an id reaction does not necessarily require discontinuing treatment and may occur before institution of therapy. among wrestlers (tinea corporis gladiatorum), where it is often limited to the neck and arms but may also involve the scalp. (2) (13)(43) This reaction should be distinguished from a drug reaction, but id reactions are much more common. (5) TINEA CORPORIS Epidemiology Tinea corporis is a dermatophyte infection of the body, often referred to as ringworm. It can be caused by any dermatophyte that infects humans. Among young children, acute infections may be caused by M canis from contact with dog or cat carriers. (2) However, in North America, it is most commonly caused by Trichophyton species, especially T tonsurans and Trichophyton rubrum. (2)(3)(4) Tinea corporis may be spread by close body contact and has been found to be more prevalent in warm and moist environments and 14 Clinical Presentation Tinea corporis presents as a single or multiple red, scaly papules (sometimes follicular) that may spread and combine, forming plaques that tend to be annular and clear in the center. (2) The plaques generally are limited to a few sites on the body and are usually unilateral (Fig 2). (2) Mild erythema, edema, vesicles, pustules, or bulla formation can occur, and the sites may be pruritic. (2) The presence of pustules and inflammation tends to be more common with infections caused by M canis whereas follicular infections are often caused by T rubrum. (2) In addition, follicular inflammatory reactions are more common among patients who have used topical corticosteroids. (2) Because the use of topical corticosteroids (eg, when atopic dermatitis is Pediatrics in Review Downloaded from http://pedsinreview.aappublications.org/ by guest on February 27, 2017

suspected) may alter the appearance of tinea corporis (tinea Diagnostic Tests incognito), physicians should use clinical judgement in Diagnosis can be confirmed with KOH microscopy or a culture, although cultures are usually not needed. obtaining a sample for KOH microscopy for annular scaly skin lesions, particularly for those lesions that have an atypical appearance. (4) Differential Diagnosis The differential diagnosis of tinea corporis includes granuloma annulare, nummular eczema, erythema multiforme, erythema annulare centrifugum, psoriasis, pityriasis rosea, subacute cutaneous or discoid lupus, atopic dermatitis, candidiasis, fixed drug eruption, early Lyme disease, and seborrheic dermatitis. (1)(2) These conditions often have several characteristics that distinguish them from tinea corporis. For example, granuloma annulare is smooth; has no scaling, vesicles, pustules, or pruritus; and is often nod- Treatment Topical antifungals are generally effective and should be used for 1 additional week after symptoms resolve. (2) Some have suggested that butenafine and terbinafine are more effective than miconazole and clotrimazole. (3) Topical corticosteroids eventually worsen the infection and should not be used. When topical treatments fail or infections recur, oral antifungals may be needed. This is often the case for those who have had prolonged pretreatment with topical corticosteroids, those who have follicular infections, and for individuals who are immunocompromised because they often have extensive and severe infections. Because tinea corporis is more common in warm and humid environments, the skin should be kept cool and dry to promote healing. (2)(4) ular (dermal with no epidermal component) and present on the dorsum of the hands or feet. (1) Histologically the epidermis is not affected; rather, inflammation is in the TINEA PEDIS dermis. (4) Nummular eczema is less likely to have central Epidemiology clearing and has more convergent scaling while erythema TP, known as athlete’s foot, is largely caused by T rubrum and Trichophyton mentagrophytes. Athlete’s foot is most common among adolescents and is relatively rare among prepubertal children. Prevalence is estimated to be approximately 3% to 9% in children. (44)(45)(46)(47)(48) Because TP is uncommon among children, it is often misdiagnosed. (49) This can be problematic because treatment with topical corticosteroids may alter the clinical appearance, making subsequent diagnosis difficult. (50) multiforme is characterized by acute-onset target lesions (sometimes oral) without scaling. (1) For additional differentiating characteristics, please refer to Ely et al (1) and Kelly. (4) Clinical Presentation Figure 2. Tinea corporis. Photo courtesy of Dr Avner Shemer, The Chaim Sheba Medical Center Israel. Symptoms of TP include erythema, scaling, fissures, maceration, and pruritus between the toes extending to the soles, borders, and sometimes the dorsum of the foot (Fig 3). Onychomycosis may occur concomitantly. (1) The 3 typical presentations are intertriginous dermatitis (interdigital), “moccasin” pattern, and vesicular. Interdigital TP is the most common presentation and is characterized by scaling (usually between the fourth and fifth toes (9) because for anatomic reasons this web space tends to be the most occluded), maceration, pruritus, and fissuring of the lateral toe web spaces that may spread to the soles and dorsum of the foot. (51) This presentation often starts in the toe web where maceration and moisture are present. (9) Moccasin TP is typically chronic and is characterized by dry scaling patches or hyperkeratotic plaques, erythema on the soles and border of the foot, and possibly tenderness or pruritus. Vol. 38 No. 1 Downloaded from http://pedsinreview.aappublications.org/ by guest on February 27, 2017 JANUARY 2017 15

Treatment Figure 3. Tinea pedis. Photo courtesy of Dr Avner Shemer, The Chaim Sheba Medical Center Israel. (51) This presentation may also involve infection of the nails (onych

2. Know the differential diagnosis of various fungal skin infections. 3. Know what diagnostic tests can be used to confirm infection. 4. Be aware of available treatment options and how to manage the infections appropriately. INTRODUCTION Candidal diaper dermatitis is the most common fungal infection of childhood.